Tian J H, Xu W, Fang Y, Han J S
Neuroscience Research Center, Beijing Medical University.
Sheng Li Xue Bao. 1997 Jun;49(3):333-8.
The discovery of a novel receptor-opioid receptor-like (ORL) receptor (1994) and its endogenous ligand-Orphanin FQ (OFQ) (1995) represented a new approach in the study of opioids and anti-opioids in CNS. Based on the high homology of ORL receptor and OFQ with their opioid family counterparts, as well as the high expression of ORL receptor mRNA and protein in the brain areas associated with nociception, the effect of OFQ on morphine induced analgesia in the rat brain was further investigated. The results showed that: (1) Intracerebroventricular (i.c.v.) injection of OFQ reversed the stress analgesia induced by i.c.v. injection of normal saline, which seems to be mediated by endogenous opioid peptides. (2) I.c.v. injection of OFQ dose-dependently antagonized morphine-induced analgesia dose-dependently. (3) I.c.v. injection of antisense oligodeoxynucleotide for the gene encoding ORL receptor to block the expression of ORL receptor in the CNS potentiated the analgesia induced by cumulative injection of morphine. The results suggest that OFQ seems to play a role of anti-opioid peptide in the rat brain.
新型受体——类阿片受体（ORL）受体的发现（1994年）及其内源性配体——孤啡肽（OFQ）的发现（1995年）代表了中枢神经系统中阿片类药物和抗阿片类药物研究的一种新方法。基于ORL受体和OFQ与其阿片类家族对应物的高度同源性，以及ORL受体mRNA和蛋白质在与伤害感受相关的脑区中的高表达，进一步研究了OFQ对大鼠脑中吗啡诱导镇痛的影响。结果表明：（1）脑室内（i.c.v.）注射OFQ可逆转脑室内注射生理盐水诱导的应激镇痛，这似乎是由内源性阿片肽介导的。（2）脑室内注射OFQ剂量依赖性地拮抗吗啡诱导的镇痛作用。（3）脑室内注射针对编码ORL受体的基因的反义寡脱氧核苷酸以阻断中枢神经系统中ORL受体的表达，可增强累积注射吗啡诱导的镇痛作用。结果表明，OFQ似乎在大鼠脑中发挥抗阿片肽的作用。
